The broad long-term objectives of this grab application are two-fold: First, new stump/socket interface materials for persons with artificial limbs will be developed. The materials will reduce the occurrence of skin breakdown and enhance skin adaption into a load-tolerant and durable tissue. Second, rehabilitative and therapeutic treatment methods to enhance skin integrity will be created. The specific aims are directed at interface mechanics, materials, and tissue response. Interface normal and shear stresses will be measured on below-knee amputee subjects during ambulation. Those data will be used to enhance an analytical model to predict interface stresses. A quantitative relationship between the magnitude and direction of interface stress and the time-to-breakdown in skin will be determined. Using both the analytical model and the quantitative relationship between interface stresses and tissue breakdown, tissue response for different prosthetic liner materials will be compared. Liners with variable material properties will be evaluated to determine if they induce a lower risk of breakdown than homogenous liners. To allow the analytical model to be extended to develop prosthetic designs and treatment strategies that induce a favorable response, i.e. cause the skin to adapt to become durable and load tolerant, basic studies on tissue adaptation to mechanical stress will be conducted. The health relatedness of the project is to improve the health and function of persons with amputations. The development of prosthetic liner and ultimately the prevention of skin breakdown will prevent secondary disability and morbidity in the amputee population. We propose to address these objectives using a combination of experimental and analytical techniques. Two types of experiments will be conducted. First, using human amputee subjects, interface stresses in clinical data collection sessions will be measured using custom- designed triaxial force transducers. Second, using an animal model, tissue response will be measured for different interface stress magnitudes and directions. Time-to-breakdown will be measured under different combinations of normal and shear stress. To evaluate adapted skin, morphological and biochemical techniques will be used to assess changes in collagen fibril diameter and crosslinking compared with control. For the analytical techniques, the finite elements modeling method will be used to predict skin stresses in amputee subjects, then extended to predict time-to-breakdown for different prosthetic liner designs.